Flowing east, it passes through the communities of Melita, Hartney, Souris, and Wawanesa, Manitoba, prior to the confluence with the Assiniboine River near Treesbank, about 40 kilometres (25 mi) southeast of Brandon.

At the end of the last ice age, over 10,000 years ago, the rapid draining of former Glacial Lake Regina eroded a large channel that is now occupied by the much smaller contemporary Souris River.

During the period from 1930 to 1941 severe drought conditions prevailed and PFRA constructed four stock watering dams.

Most of the annual flow of the Souris River comes from snow melt and spring rains.

The average annual runoff is equivalent to 3 mm over the entire Souris River watershed.